Gene Expression in the Brain and Suicide

Gustavo Turecki, M.D., Ph.D.

Gustavo Turecki, M.D., Ph.D., has received his second AFSP Distinguished Investigator award and has mentored many AFSP researchers throughout his career. He has dedicated his efforts to identifying brain mechanisms for suicide, specifically the neurobiological changes that result from early life stress and adversity and increase the risk for suicide.

By studying microRNA’s in the brains of people who died by suicide and comparing them with the brains of people who died by other means, Dr. Turecki is working to explain how genes work in different parts of the brain to effect behavior. MicroRNA’s are small molecules of RNA that function to regulate the expression of genes by telling them when to turn on and turn off as well as to increase and decrease in number. Results of his study were published in June 2012 in PLOS ONE from the Public Library of Science. For this paper, 55 individuals were studied, 38 who died by suicide and 17 who died by other causes. About 60% of those who died by suicide had a documented history of major depression. Diagnoses were determined by using the psychological autopsy method by which close family members or friends are interviewed with a structured interview by a trained clinician about the deceased and medical and coroner records are reviewed.

The specific microRNA studied was TrkB-T1 in the frontal cortex because it has been shown to be present at lower rates in those who died by suicide than in others. The frontal cortex is specifically involved in the organization and inhibition of behavior and lowered functioning has been found to relate to rigid thinking and impulsiveness. In a series of experiments, the investigators demonstrated that TrkB-T1 was lower in frontal cortex of suicides and not in other brain areas. They showed that Has-miR-185, a microRNA suspected of controlling TrkB-T1, was found to be increased in the frontal lobe when TrkB-T1 was low suggesting a relationship between the two.

This study begins to tackle complicated genetic relationships in the brain. It serves as a model for other researchers and we hope that understanding these differences will help to develop assessments and treatments for individuals at risk.

Gustavo Turecki, M.D., Ph.D., is the Director of the McGill Group for Suicide Studies and the Quebec Suicide Brain Bank in Montreal Canada. He was bestowed the AFSP Annual Research Award in 2012. Click here to read more about Dr. Turecki's Distinguished Investigator Grant.